Affinage

SERPINB3

Serpin B3 · UniProt P29508

Length
390 aa
Mass
44.6 kDa
Annotated
2026-04-28
100 papers in source corpus 22 papers cited in narrative 21 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SERPINB3 (SCCA1) is a cross-class intracellular serpin that inhibits papain-like cysteine proteases and modulates kinase signaling, tumor immunity, and epithelial barrier function. Its reactive site loop (RSL) is both necessary and sufficient for inhibition of cathepsins L, S, and K, and RSL-swap experiments demonstrate that the RSL sequence dictates target specificity between SERPINB3 and its paralog SERPINB4 (PMID:9811823, PMID:9817977); the RSL also mediates suppression of JNK1 kinase activity through a partially distinct mechanism (PMID:19166818). In cancer, SERPINB3 promotes tumor survival by inhibiting cathepsin L–mediated lysoptosis and calpain-mediated MYC degradation, activating a sustained unfolded protein response that drives NF-κB/IL-6 signaling, and inducing STAT-dependent chemokine production (CXCL1/8, S100A8/A9) that recruits immunosuppressive myeloid cells (PMID:35022555, PMID:37980563, PMID:24759783, PMID:37279067). SERPINB3 also contributes to epithelial barrier dysfunction and inflammatory responses in skin, as Serpinb3a-null mice show attenuated allergen-induced epidermal inflammation (PMID:25111616).

Mechanistic history

Synthesis pass · year-by-year structured walk · 9 steps
  1. 1998 High

    Establishing the core enzymatic identity: SERPINB3 was shown to be a cross-class inhibitor of papain-like cysteine cathepsins (L, S, K), with the RSL as the essential determinant of target specificity, resolving how two nearly identical paralogs (SERPINB3/B4) inhibit different protease classes.

    Evidence Recombinant protein kinetics, RSL mutagenesis and domain-swap experiments between SCCA1 and SCCA2 in vitro

    PMID:9811823 PMID:9817977 PMID:9817978

    Open questions at the time
    • No cellular validation of cathepsin inhibition in intact cells
    • Stoichiometry and kinetics of the serpin–cathepsin complex not fully resolved structurally
  2. 2009 High

    Expanding SERPINB3 function beyond protease inhibition: the crystal structure revealed that the RSL also mediates suppression of JNK1 kinase activity, but a point mutation separating protease from kinase inhibition showed the two activities are mechanistically overlapping yet distinct.

    Evidence X-ray crystallography, RCL truncation and point mutants, in vitro JNK1 kinase assay

    PMID:19166818

    Open questions at the time
    • JNK1 inhibition not validated in cellular context
    • Binding mode of SERPINB3 to JNK1 not structurally determined
    • Physiological relevance of JNK1 suppression unclear
  3. 2010 High

    Linking SERPINB3 to epithelial plasticity and growth factor regulation: SERPINB3 induced EMT in hepatocytes through a protease-independent paracrine/autocrine mechanism, while separately inducing TGF-β1 expression through its protease-inhibitory RSL, demonstrating that SERPINB3 engages both protease-dependent and protease-independent pro-tumorigenic pathways.

    Evidence Stable overexpression, RSL-deleted mutant protein, invasion/migration assays, TGF-β1 mRNA/protein quantification in hepatoma cells

    PMID:20212457 PMID:20527027

    Open questions at the time
    • Receptor or signaling pathway mediating protease-independent EMT not identified
    • TGF-β1 induction mechanism downstream of RSL not defined
  4. 2014 High

    Establishing the oncogenic signaling axis: oncogenic Ras transcriptionally upregulates SERPINB3 via PEA3, and SERPINB3 in turn inhibits protein turnover, triggers a sustained unfolded protein response (UPR), and activates NF-κB/IL-6 signaling to promote tumor growth — positioning SERPINB3 as an effector linking Ras to protumorigenic inflammation.

    Evidence Knockdown/overexpression, PEA3 reporter assays, UPR and NF-κB pathway analysis, xenograft models, human colorectal and breast cancer samples

    PMID:24759783 PMID:25213322

    Open questions at the time
    • Direct UPR-activating mechanism (substrate accumulation vs. ER stress sensor engagement) not dissected
    • Whether NF-κB activation requires protease-inhibitory activity not tested
  5. 2014 High

    Extending SERPINB3 function to non-malignant epithelial inflammation: Serpinb3a knockout mice showed attenuated allergen-induced barrier disruption and inflammation, and SERPINB3/B4 silencing reduced S100A8 expression in keratinocytes, establishing a role in atopic dermatitis pathogenesis.

    Evidence Serpinb3a knockout mice, allergen challenge, TEWL measurement, RNA-seq, siRNA in human keratinocytes

    PMID:25111616

    Open questions at the time
    • Which protease target mediates the barrier phenotype not identified
    • Relative contributions of SERPINB3 vs. SERPINB4 in skin barrier not resolved
  6. 2015 Medium

    Identifying a hypoxic regulatory circuit: HIF-2α (not HIF-1α) directly binds the SERPINB3 promoter under hypoxia in an ROS-dependent manner, and conversely SERPINB3 promotes HIF-2α stabilization via selective NEDDylation, creating a positive feedback loop in hepatocellular carcinoma.

    Evidence ChIP assay, siRNA knockdown of HIF-1α/HIF-2α, hypoxia exposure, transgenic/knockout mice, NEDDylation pathway analysis

    PMID:25544768 PMID:31817100

    Open questions at the time
    • Mechanism by which SERPINB3 promotes NEDDylation of HIF-2α not biochemically defined
    • NEDDylation finding from single lab awaits independent confirmation
  7. 2022 High

    Pinpointing cathepsin L–mediated lysoptosis as a key death pathway suppressed by SERPINB3: genetic knockout sensitized cervical cancer and glioblastoma stem cells to radiation-induced necrotic/lysosomal cell death, and rescue required intact RSL protease-inhibitory activity, firmly connecting the serpin's anti-protease function to radioresistance.

    Evidence CRISPR knockout, RSL-mutant rescue, radiation sensitivity assays, cathepsin L genetic studies, shRNA in glioblastoma CSCs with in vivo tumor models

    PMID:35022555 PMID:36103817

    Open questions at the time
    • Whether other lysosomal proteases contribute to lysoptosis resistance not tested
    • Structural basis of SERPINB3–cathepsin L complex in lysosomes not resolved
  8. 2022 Medium

    Revealing a DNA repair–related function: SERPINB3 supports USP1-mediated deubiquitination of FANCD2-FANCI in the Fanconi anemia pathway, thereby promoting cisplatin interstrand crosslink repair and chemoresistance in HNSCC.

    Evidence Knockdown/overexpression, FANCD2-FANCI ubiquitination analysis, cisplatin sensitivity assays, patient-derived xenograft with siRNA nanoparticles

    PMID:36382555

    Open questions at the time
    • Direct physical interaction between SERPINB3 and USP1 not demonstrated
    • Whether this function requires protease-inhibitory activity not tested
    • Single-lab finding awaiting independent replication
  9. 2023 High

    Defining immunosuppressive and metabolic effector mechanisms: SERPINB3 inhibits calpain to stabilize MYC (driving squamous transcriptional programs and metabolic reprogramming), and independently induces STAT-dependent CXCL1/8 and S100A8/A9 to recruit MDSCs and M2 macrophages, creating an immunosuppressive tumor microenvironment.

    Evidence Transgenic overexpression, xenograft/syngeneic tumor models, metabolomics, RNA-seq, STAT inhibitor (ruxolitinib) treatment, flow cytometry of immune infiltrates

    PMID:37279067 PMID:37980563

    Open questions at the time
    • Whether calpain inhibition and STAT-dependent chemokine induction are mechanistically linked or independent arms not resolved
    • Specific calpain isoform(s) targeted by SERPINB3 not identified

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key open questions: the structural basis of SERPINB3 interactions with non-protease partners (JNK1, USP1/FANCD2, calpain) remains undefined; the protease-independent EMT mechanism lacks a receptor or signaling pathway; and whether the UPR, immunosuppression, and DNA repair functions are interconnected or represent parallel arms has not been tested.
  • No co-crystal structure of SERPINB3 with any non-protease partner
  • Protease-independent signaling pathway for EMT unidentified
  • Integration of UPR, immune modulation, and DNA repair functions not addressed

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 6 GO:0140096 catalytic activity, acting on a protein 5
Localization
GO:0005829 cytosol 3 GO:0005576 extracellular region 2
Pathway
R-HSA-1643685 Disease 5 R-HSA-162582 Signal Transduction 4 R-HSA-168256 Immune System 3 R-HSA-5357801 Programmed Cell Death 2 R-HSA-73894 DNA Repair 1
Partners
CAPN1CTSKCTSLCTSSFANCD2MAPK8MYCUSP1

Evidence

Reading pass · 21 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 SCCA1 (SERPINB3) inhibits papain-like cysteine proteinases (cathepsins L, S, K) and this inhibitory activity is fully dependent on the reactive site loop (RSL); RSL swaps between SCCA1 and SCCA2 reversed their target specificities, demonstrating that the RSL sequence and mobility are essential for cysteine proteinase inhibition. Site-directed mutagenesis of RSL residues, RSL swap experiments between SCCA1 and SCCA2, in vitro protease inhibition assays Proceedings of the National Academy of Sciences of the United States of America High 9811823
1998 SCCA1 (SERPINB3) is a potent cross-class inhibitor of papain-like cysteine proteinases (cathepsins L, S, K), while SCCA2 (SERPINB4) inhibits chymotrypsin-like serine proteinases (cathepsin G, mast cell chymase); the two paralogs map to 18q21.3. Biochemical analysis of recombinant SCCA1 and SCCA2 proteins; in vitro protease inhibition assays Tumour biology High 9817977 9817978
2009 Crystal structure of SCCA1 (SERPINB3) revealed a flexible reactive center loop (RCL) located away from the main body; truncation of the RCL abolished SCCA1's inhibitory effect on JNK1 kinase activity, and a single RCL point mutation that reduced protease inhibition retained JNK1 suppression, indicating the RCL mediates both protease and JNK1 inhibition through partially overlapping but distinct mechanisms. X-ray crystallography, RCL truncation mutants, in vitro JNK1 kinase activity assay Biochemical and biophysical research communications High 19166818
2010 SERPINB3 induces epithelial-mesenchymal transition (EMT) in HepG2 cells, characterized by reduced E-cadherin, increased beta-catenin and vimentin, loss of desmosomal junctions, and increased cell migration and invasiveness; these effects occurred at both autocrine and paracrine levels and did not require anti-protease activity, as an active-loop-deleted recombinant SERPINB3 retained EMT-inducing activity. Stable transfection of HepG2 cells with SERPINB3 gene, exogenous recombinant SERPINB3 treatment of HepG2 and MDCK cells, active-loop-deleted mutant protein, morphological/ultrastructural analysis, western blot, invasion and migration assays, soft agar colony formation The Journal of pathology High 20527027
2010 SERPINB3 modulates TGF-beta1 expression in hepatocytes; transfection with intact SERPINB3 increased TGF-beta1 mRNA and protein, and this effect required an intact reactive site loop, implicating the anti-protease activity in TGF-beta1 induction. Transfection of hepatocytes and hepatoma cell lines (HepG2, Huh7) with SERPINB3 or reactive-site-loop-deleted mutants, real-time PCR, ELISA, correlation with liver biopsy data Laboratory investigation Medium 20212457
2014 Oncogenic Ras transcriptionally upregulates SERPINB3 (SCCA1) via the MAPK pathway and ETS transcription factor PEA3; elevated SCCA1 inhibits protein turnover, activates the unfolded protein response (UPR) and NF-κB, and is required for Ras-mediated cytokine production and tumor growth. Genetic knockdown and overexpression in cell lines, reporter assays for PEA3 binding, UPR markers, NF-κB assays, xenograft tumor growth assays, analysis of human colorectal and pancreatic tumor samples Nature communications High 24759783
2014 SCCA1 (SERPINB3) promotes oncogenic transformation and EMT in mammary epithelial cells and drives a prolonged non-lethal UPR that activates NF-κB and IL-6 autocrine signaling, contributing to protumorigenic inflammation. Stable overexpression and siRNA knockdown in mammary epithelial and breast cancer cells, UPR marker analysis, NF-κB reporter assays, IL-6 ELISA, neu+ mammary tumor mouse model Cancer research High 25213322
2015 Hypoxia upregulates SERPINB3 transcription, protein synthesis, and secretion in hepatocellular carcinoma cells selectively through HIF-2α (not HIF-1α) binding to the SERPINB3 promoter, in a process requiring intracellular ROS generation. Chromatin immunoprecipitation (ChIP) assay, siRNA silencing of HIF-1α and HIF-2α, hypoxia exposure of HepG2 and Huh7 cells, RT-PCR, western blot, immunohistochemistry of human HCC specimens Oncotarget High 25544768
2011 The polymorphic SERPINB3 variant SCCA-PD (Gly351Ala in the reactive center loop) exhibits increased inhibitory activity against papain and cathepsin L compared to wild-type SERPINB3, and also shows a 16% higher inhibitory effect on JNK1 kinase activity at high concentration; 3D modeling indicates increased hydrophobic character at the mutation site. Kinetic analysis with recombinant proteins, in vitro protease inhibition assays, JNK1 kinase inhibition assay, crystal structure-based 3D modeling Experimental biology and medicine Medium 21383048
2014 SERPINB3 and SERPINB4 contribute to epidermal barrier dysfunction and early inflammatory response in atopic dermatitis; Serpinb3a-null mice showed attenuated transepidermal water loss, epidermal thickening, and inflammation after allergen exposure, and SERPINB3/B4 silencing in human keratinocytes decreased S100A8 expression. Serpinb3a knockout mice, topical allergen challenge model, TEWL measurement, RNA-seq, siRNA knockdown in human keratinocytes The Journal of investigative dermatology High 25111616
2022 SERPINB3 protects cervical cancer cells from ionizing radiation-induced cell death by inhibiting cathepsin L-mediated lysoptosis; SERPINB3 knockout sensitizes cells to IR-induced necrotic death, and rescue with wild-type but not a reactive-site-loop mutant SERPINB3 restored protection, demonstrating the requirement for protease inhibitory activity. SERPINB3 genetic knockout, wild-type and RSL-mutant rescue, ionizing radiation treatment, cell death assays (necrosis/lysoptosis markers), transcriptomics, cathepsin L genetic studies Communications biology High 35022555
2022 SerpinB3 is necessary for glioblastoma cancer stem cell (CSC) maintenance, survival, and tumor growth by buffering cathepsin L-mediated cell death; SerpinB3 knockdown increased apoptosis, enhanced radiation sensitivity, and reduced tumor growth in pre-clinical models. Genetic depletion (shRNA knockdown), apoptosis assays, cathepsin L functional studies, radiation sensitivity assays, in vivo tumor growth models Cell reports High 36103817
2023 SERPINB3 inhibits the cysteine protease calpain, a key enzyme in the MYC degradation pathway, thereby stabilizing MYC and driving the basal-like/squamous transcriptional subtype and associated metabolic reprogramming (elevated carnitine/acylcarnitine and amino acid metabolism) in pancreatic cancer; SERPINB3 transgene expression enhanced in vitro invasion and promoted lung metastasis in mouse xenografts. SERPINB3 transgene overexpression, xenograft mouse model, metabolome analysis, calpain-MYC degradation pathway analysis, transcriptome analysis Cell reports High 37980563
2023 SERPINB3 promotes immunosuppression by inducing STAT-dependent expression of chemokines CXCL1/8 and S100A8/A9, which promotes monocyte and myeloid-derived suppressor cell (MDSC) migration; intratumoral knockdown of Serpinb3a reduced MDSC and M2 macrophage infiltration, enhanced cytotoxic T cell function, and sensitized tumors to radiotherapy. RNA-seq of human cervical tumors, SERPINB3 overexpression and knockdown in cell lines and mouse tumor models, STAT inhibitor (ruxolitinib) and siRNA experiments, flow cytometry, in vitro migration assays The Journal of clinical investigation High 37279067
2019 MiR-122 directly targets SERPINB3 mRNA; miR-122 transfection decreased SERPINB3 mRNA and protein in SERPINB3-overexpressing HepG2 cells, confirmed by luciferase reporter assay; low miR-122 levels correlate with SERPINB3 positivity and sorafenib resistance in HCC. miR-122 transfection and inhibition in hepatoma cells, luciferase reporter assay, bioinformatics, HCC rat model, human patient data Journal of clinical medicine Medium 30717317
2022 SERPINB3 confers cisplatin resistance in HNSCC by supporting USP1-mediated deubiquitination of FANCD2-FANCI in the Fanconi anemia DNA repair pathway; downregulation of SERPINB3 reduces FANCD2-FANCI deubiquitination, impairs repair of cisplatin-induced DNA interstrand crosslinks, and enhances cisplatin-induced apoptosis. SERPINB3 knockdown and overexpression, cisplatin sensitivity assays, FANCD2-FANCI ubiquitination analysis, patient-derived xenograft model with siRNA nanoparticle delivery Advanced science Medium 36382555
2019 SerpinB3 acts as a paracrine mediator that differentially upregulates HIF-1α (at the transcriptional level, promoting angiogenesis and cell survival) and HIF-2α (by direct/selective NEDDylation, promoting proliferation) in hepatocellular carcinoma cells under normoxic conditions. SerpinB3 transgenic and knockout mice, hepatoma cell lines, DEN/CDAA carcinogenic mouse model, NAE1 mRNA analysis, immunohistochemistry of human HCC, NEDDylation pathway analysis Cancers Medium 31817100
2014 TEAD4 transcriptionally regulates SERPINB3/B4 expression in psoriatic keratinocytes; SERPINB3/B4 depletion inhibited chemokine secretion from keratinocytes, reducing T cell migration, establishing TEAD4-SERPINB3/B4 as a regulatory axis in keratinocyte-T cell crosstalk in psoriasis. TEAD4 knockdown, SERPINB3/B4 siRNA silencing in psoriatic keratinocytes, chemokine secretion assays, T cell migration assay Immunobiology Medium 32962824
2014 SerpinB3 is expressed in hepatic progenitor cells (EpCAM-positive cells) in both fetal and adult liver, and is induced in a mouse model of liver progenitor cell activation following LPS/D-galactosamine injury, with parallel decrease in activated caspase-3. FACS sorting of EpCAM+ liver cells, immunohistochemistry, RT-PCR and sequencing in mouse model, time-course analysis BMC cell biology Medium 24517394
2014 SerpinB3 binds to respiratory Complex I, protecting cancer cells from the pro-oxidant action of chemotherapeutic agents and contributing to drug resistance. Referenced in review (PMID 25332258) but not directly demonstrated in a primary experimental paper in this corpus Annals of hepatology Low 25332258
2014 Pso p27, an autoantigen in psoriasis, is generated from SCCA1 (SERPINB3) by mast cell chymase cleavage; the resulting fragments remain associated as a complex with novel immunogenic properties and increased aggregation tendency. In vitro digestion of SCCA1 with psoriatic scale extracts and purified mast cell chymase, protein characterization Biochimica et biophysica acta Medium 24560885

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2003 Insights on antibiotic resistance of Staphylococcus aureus from its whole genome: genomic island SCC. Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy 270 12654286
2018 The genomic landscape of cutaneous SCC reveals drivers and a novel azathioprine associated mutational signature. Nature communications 235 30202019
1987 Gene structure of human cytochrome P-450(SCC), cholesterol desmolase. Journal of biochemistry 183 3038854
2011 Tumor-associated macrophages in the cutaneous SCC microenvironment are heterogeneously activated. The Journal of investigative dermatology 145 21307877
2004 Expression of SCC-S2, an antiapoptotic molecule, correlates with enhanced proliferation and tumorigenicity of MDA-MB 435 cells. Oncogene 104 14724590
1995 CEA, CYFRA21-1 and SCC in non-small cell lung cancer. Lung cancer (Amsterdam, Netherlands) 97 8581396
2009 SERPINB3, apoptosis and autoimmunity. Autoimmunity reviews 87 19332150
2016 SERPINB3 and B4: From biochemistry to biology. Seminars in cell & developmental biology 85 27637160
1996 Stoichiometry and domainal organization of the long tail-fiber of bacteriophage T4: a hinged viral adhesin. Journal of molecular biology 85 8709154
2014 SERPINB3/B4 contributes to early inflammation and barrier dysfunction in an experimental murine model of atopic dermatitis. The Journal of investigative dermatology 77 25111616
2015 Suppression of TGFβ and Angiogenesis by Type VII Collagen in Cutaneous SCC. Journal of the National Cancer Institute 76 26476432
2010 SERPINB3 induces epithelial-mesenchymal transition. The Journal of pathology 75 20527027
2014 Oncogenic Ras induces inflammatory cytokine production by upregulating the squamous cell carcinoma antigens SerpinB3/B4. Nature communications 72 24759783
1998 The reactive site loop of the serpin SCCA1 is essential for cysteine proteinase inhibition. Proceedings of the National Academy of Sciences of the United States of America 70 9811823
2019 The role of squamous cell carcinoma antigen (SCC Ag) in outcome prediction after concurrent chemoradiotherapy and treatment decisions for patients with cervical cancer. Radiation oncology (London, England) 65 31416463
1998 SCC antigen in malignant and nonmalignant squamous lesions. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 63 9817981
2014 SCCA1/SERPINB3 promotes oncogenesis and epithelial-mesenchymal transition via the unfolded protein response and IL6 signaling. Cancer research 60 25213322
2007 Restriction endonuclease inhibitor IPI* of bacteriophage T4: a novel structure for a dedicated target. Journal of molecular biology 60 18037438
1999 Tissue-specific, hormonal, and developmental regulation of SCC-LacZ expression in transgenic mice leads to adrenocortical zone characterization. Endocrinology 53 10579324
2015 Hypoxia up-regulates SERPINB3 through HIF-2α in human liver cancer cells. Oncotarget 49 25544768
2011 Loading of meiotic cohesin by SCC-2 is required for early processing of DSBs and for the DNA damage checkpoint. Current biology : CB 48 21856158
2003 Caenorhabditis elegans EVL-14/PDS-5 and SCC-3 are essential for sister chromatid cohesion in meiosis and mitosis. Molecular and cellular biology 48 14560015
1994 Immunocytochemical localization of fibroblast growth factor-1 (FGF-1) and FGF-2 in oral squamous cell carcinoma (SCC). Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology 48 7532220
1997 Diagnostic value of SCC, CEA and CYFRA 21.1 in lung cancer: a Bayesian analysis. The European respiratory journal 46 9072992
2010 SERPINB3 modulates TGF-beta expression in chronic liver disease. Laboratory investigation; a journal of technical methods and pathology 43 20212457
2003 CYP1A1 and XRCC1 gene polymorphisms in SCC of the larynx. European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP) 42 14639127
2012 Novel processed form of syndecan-1 shed from SCC-9 cells plays a role in cell migration. PloS one 41 22905270
1998 Biological role of SCC antigen. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 41 9817978
2019 MiR-122 Targets SerpinB3 and Is Involved in Sorafenib Resistance in Hepatocellular Carcinoma. Journal of clinical medicine 40 30717317
2006 Overexpression of the Axl tyrosine kinase receptor in cutaneous SCC-derived cell lines and tumours. British journal of cancer 40 16641895
2020 Machine Learning Based Radiomic HPV Phenotyping of Oropharyngeal SCC: A Feasibility Study Using MRI. The Laryngoscope 37 33070337
2023 SERPINB3-MYC axis induces the basal-like/squamous subtype and enhances disease progression in pancreatic cancer. Cell reports 35 37980563
1992 Expression of mRNA of SCC antigen in squamous cells. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 35 1290029
2011 Over-expression of SERPINB3 in hepatoblastoma: a possible insight into the genesis of this tumour? European journal of cancer (Oxford, England : 1990) 34 21737255
1998 SCCA1 and SCCA2 are proteinase inhibitors that map to the serpin cluster at 18q21.3. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 31 9817977
1998 Bacteriophage T4, a model system for understanding the mechanism of type II topoisomerase inhibitors. Biochimica et biophysica acta 30 9748648
2018 The genomic landscape of UM-SCC oral cavity squamous cell carcinoma cell lines. Oral oncology 29 30527230
2015 Sirolimus use and risk of cutaneous squamous cell carcinoma (SCC) in solid organ transplant recipients (SOTRs). Journal of the American Academy of Dermatology 28 26138646
2023 SCCA1/SERPINB3 suppresses antitumor immunity and blunts therapy-induced T cell responses via STAT-dependent chemokine production. The Journal of clinical investigation 27 37279067
2022 SERPINB3 (SCCA1) inhibits cathepsin L and lysoptosis, protecting cervical cancer cells from chemoradiation. Communications biology 27 35022555
2014 Imiquimod induces apoptosis of squamous cell carcinoma (SCC) cells via regulation of A20. PloS one 27 24743316
1999 Immunocytochemical detection of hMSH2 and hMLH1 expression in oral SCC. Anticancer research 27 10368636
2019 SerpinB3 Differently Up-Regulates Hypoxia Inducible Factors -1α and -2α in Hepatocellular Carcinoma: Mechanisms Revealing Novel Potential Therapeutic Targets. Cancers 26 31817100
2006 Angucyclines Sch 47554 and Sch 47555 from Streptomyces sp. SCC-2136: cloning, sequencing, and characterization. Molecules and cells 26 17085966
2021 The Tumor Microenvironment in SCC: Mechanisms and Therapeutic Opportunities. Frontiers in cell and developmental biology 25 33634137
2020 Epidemiology and Patient Distribution of Oral Cavity and Oropharyngeal SCC in Canada. Journal of cutaneous medicine and surgery 25 32238063
2016 Pso p27, a SERPINB3/B4-derived protein, is most likely a common autoantigen in chronic inflammatory diseases. Clinical immunology (Orlando, Fla.) 25 27871892
2012 SCC-S2 is overexpressed in colon cancers and regulates cell proliferation. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 25 22886548
2001 Comparison of Cyfra 21-1 and SCC assays in head and neck tumours. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 25 11054024
2012 E-cadherin in oral SCC: an analysis of the confusing literature and new insights related to its immunohistochemical expression. Histology and histopathology 24 22207548
2022 SerpinB3 drives cancer stem cell survival in glioblastoma. Cell reports 23 36103817
2019 Pten loss in Lgr5+ hair follicle stem cells promotes SCC development. Theranostics 23 31754399
2010 Differential effects of periopathogens on host protease inhibitors SLPI, elafin, SCCA1, and SCCA2. Journal of oral microbiology 23 21523231
1998 Factors regulating SCC antigen expression in squamous cell carcinoma of the uterine cervix. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 23 9817979
2021 The protease-inhibitor SerpinB3 as a critical modulator of the stem-like subset in human cholangiocarcinoma. Liver international : official journal of the International Association for the Study of the Liver 22 34478594
2019 Antitumor Effect of Albendazole on Cutaneous Squamous Cell Carcinoma (SCC) Cells. BioMed research international 22 31281836
2009 Crystal structure of SCCA1 and insight about the interaction with JNK1. Biochemical and biophysical research communications 22 19166818
2006 The scc spirochetal coiled-coil protein forms helix-like filaments and binds to nucleic acids generating nucleoprotein structures. Journal of bacteriology 22 16385037
2016 ALA-PDT inhibits proliferation and promotes apoptosis of SCC cells through STAT3 signal pathway. Photodiagnosis and photodynamic therapy 21 26805005
2014 Role of SERPINB3 in hepatocellular carcinoma. Annals of hepatology 21 25332258
2010 Up-regulation of serpin SCCA1 is associated with epidermal barrier disruption. Journal of dermatological science 21 20089382
2005 VEGF-subtype specific protection of SCC and HUVECs from radiation induced cell death. International journal of molecular medicine 21 15583841
1992 Expression of CEA, CA-125 and SCC antigen by biological fluids associated with pregnancy. European journal of obstetrics, gynecology, and reproductive biology 21 1607061
2017 ERK1/2, JNK and STAT3 activation and correlation with tumor differentiation in oral SCC. Histology and histopathology 20 28090628
2014 Hepatic progenitor cells express SerpinB3. BMC cell biology 20 24517394
2014 The molecular signature of impaired diabetic wound healing identifies serpinB3 as a healing biomarker. Diabetologia 20 24962668
1991 Different behaviors in the production and release of SCC antigen in squamous-cell carcinoma. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 18 1705047
2019 Tumor Suppressive Function of NQO1 in Cutaneous Squamous Cell Carcinoma (SCC) Cells. BioMed research international 17 31886179
2017 Acacia catechu Ethanolic Seed Extract Triggers Apoptosis of SCC-25 Cells. Pharmacognosy magazine 17 29142391
2016 Management of BCC and SCC of the Head and Neck. Cancer control : journal of the Moffitt Cancer Center 17 27556662
2014 Raman spectroscopy differentiates squamous cell carcinoma (SCC) from normal skin following treatment with a high-powered CO2 laser. Lasers in surgery and medicine 17 25345858
2012 IgM-linked SerpinB3 and SerpinB4 in sera of patients with chronic liver disease. PloS one 17 22808225
2011 Increased antiprotease activity of the SERPINB3 polymorphic variant SCCA-PD. Experimental biology and medicine (Maywood, N.J.) 17 21383048
2022 HPV Enhances HNSCC Chemosensitization by Inhibiting SERPINB3 Expression to Disrupt the Fanconi Anemia Pathway. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 16 36382555
2017 Effects of microRNA-374 on proliferation, migration, invasion, and apoptosis of human SCC cells by targeting Gadd45a through P53 signaling pathway. Bioscience reports 16 28679648
2009 Paratuberculosis sero-status and milk production, SCC and calving interval in Irish dairy herds. Irish veterinary journal 16 21851733
2019 Immunotherapy and other systemic therapies for cutaneous SCC. Oral oncology 15 31715538
2015 Frequency of squamous cell carcinoma (SCC) invasion in transected SCC in situ referred for Mohs surgery: the Dartmouth-Hitchcock experience. International journal of dermatology 15 25920731
2002 Beyond the ABCs of CKC and SCC. Do centromeres orchestrate sister chromatid cohesion or vice versa? European journal of biochemistry 15 11985612
2023 SERPINB3, Adult-Onset Immunodeficiency, and Generalized Pustular Psoriasis. Genes 14 36833193
2021 Impact of HSP90α, CEA, NSE, SCC, and CYFRA21-1 on Lung Cancer Patients. Journal of healthcare engineering 14 34721827
2017 Diagnostic specificity and sensitivity of PIVKAII, GP3, CSTB, SCCA1 and HGF for the diagnosis of hepatocellular carcinoma in patients with alcoholic liver cirrhosis. Annals of clinical biochemistry 14 28766361
2014 MicroRNAs and SerpinB3 in hepatocellular carcinoma. Life sciences 14 24496037
2003 Comparing genomic and histologic correlations to radiographic changes in tumors: a murine SCC VII model study. Academic radiology 14 14587635
1998 Tumour-associated antigens CEA, CA125, SCC and TPS in gynaecological cancer. European journal of gynaecological oncology 14 9476065
1985 Bacteriophage T4, a new vector for the expression of cloned genes. Gene 14 3932131
2020 TEAD4 transcriptional regulates SERPINB3/4 and affect crosstalk between keratinocytes and T cells in psoriasis. Immunobiology 13 32962824
2018 Squamous Cell Carcinoma Antigen-encoding Genes SERPINB3/B4 as Potentially Useful Markers for the Stratification of HNSCC Tumours. Anticancer research 13 29491058
2022 High p62 expression suppresses the NLRP1 inflammasome and increases stress resistance in cutaneous SCC cells. Cell death & disease 12 36581625
2017 Prophylactic dissection of level V in primary mucosal SCC in the clinically N positive neck: A systematic review. The Laryngoscope 12 28411387
2015 Tumstatin induces apoptosis mediated by Fas signaling pathway in oral squamous cell carcinoma SCC-VII cells. Oncology letters 12 26622617
1998 Endonuclease II of coliphage T4: a recombinase disguised as a restriction endonuclease? Molecular microbiology 12 9515694
2021 SCC: an accurate imputation method for scRNA-seq dropouts based on a mixture model. BMC bioinformatics 11 33407064
2018 SerpinB3 induces dipeptidyl-peptidase IV/CD26 expression and its metabolic effects in hepatocellular carcinoma. Life sciences 11 29524519
2021 Low P66shc with High SerpinB3 Levels Favors Necroptosis and Better Survival in Hepatocellular Carcinoma. Biology 10 33922660
2015 Serum and Saliva MMP-3 in Patients with OLP and Oral SCC. The journal of contemporary dental practice 10 25906800
2014 Psoriasis pathogenesis - Pso p27 is generated from SCCA1 with chymase. Biochimica et biophysica acta 10 24560885
2011 Tissue specific expression and estrogen regulation of SERPINB3 in the chicken oviduct. General and comparative endocrinology 10 22026959
2008 Squamous cell carcinoma antigen-1 (SERPINB3) polymorphism in chronic liver disease. Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver 10 18657489
2001 Expression of SCC in ovarian granulosa cells and cultured cells, induced rapid structural changes in mitochondria. Italian journal of anatomy and embryology = Archivio italiano di anatomia ed embriologia 10 11729997